Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes

Franco Cosmi; Li Shen; Michela Magnoli; William T. Abraham; Inder S. Anand; John G. Cleland; Jay N. Cohn; Deborah Cosmi; Giorgia De Berardis; Kenneth Dickstein; Maria Grazia Franzosi; Lars Gullestad; Pardeep S. Jhund; John Kjekshus; Lars Køber; Vito Lepore; Giuseppe Lucisano; Aldo P. Maggioni; Serge Masson; John J.V. McMurray; Antonio Nicolucci; Vito Petrarolo; Fabio Robusto; Lidia Staszewsky; Luigi Tavazzi; Roberto Teli; Gianni Tognoni; John Wikstrand; Roberto Latini

doi:10.1002/ejhf.1146

Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes

Franco Cosmi, Li Shen, Michela Magnoli, William T. Abraham, Inder S. Anand, John G. Cleland, Jay N. Cohn, Deborah Cosmi, Giorgia De Berardis, Kenneth Dickstein, Maria Grazia Franzosi, Lars Gullestad, Pardeep S. Jhund, John Kjekshus, Lars Køber, Vito Lepore, Giuseppe Lucisano, Aldo P. Maggioni, Serge Masson, John J.V. McMurrayAntonio Nicolucci, Vito Petrarolo, Fabio Robusto, Lidia Staszewsky, Luigi Tavazzi, Roberto Teli, Gianni Tognoni, John Wikstrand, Roberto Latini^*

^*Corresponding author for this work

Department of Clinical Medicine

43 Citations (Scopus)

Abstract

Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.

Original language	English
Journal	European Journal of Heart Failure
Volume	20
Issue number	5
Pages (from-to)	888-895
Number of pages	8
ISSN	1388-9842
DOIs	https://doi.org/10.1002/ejhf.1146
Publication status	Published - 2018

Keywords

Diabetes mellitus
Heart failure
Insulin

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cosmi, F., Shen, L., Magnoli, M., Abraham, W. T., Anand, I. S., Cleland, J. G., Cohn, J. N., Cosmi, D., De Berardis, G., Dickstein, K., Franzosi, M. G., Gullestad, L., Jhund, P. S., Kjekshus, J., Køber, L., Lepore, V., Lucisano, G., Maggioni, A. P., Masson, S., ... Latini, R. (2018). Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes. European Journal of Heart Failure, 20(5), 888-895. https://doi.org/10.1002/ejhf.1146

Cosmi, F, Shen, L, Magnoli, M, Abraham, WT, Anand, IS, Cleland, JG, Cohn, JN, Cosmi, D, De Berardis, G, Dickstein, K, Franzosi, MG, Gullestad, L, Jhund, PS, Kjekshus, J, Køber, L, Lepore, V, Lucisano, G, Maggioni, AP, Masson, S, McMurray, JJV, Nicolucci, A, Petrarolo, V, Robusto, F, Staszewsky, L, Tavazzi, L, Teli, R, Tognoni, G, Wikstrand, J & Latini, R 2018, 'Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes', European Journal of Heart Failure, vol. 20, no. 5, pp. 888-895. https://doi.org/10.1002/ejhf.1146

@article{f8c7617c129d4e5aa063f8ec03e15418,

title = "Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes",

abstract = "Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.",

keywords = "Diabetes mellitus, Heart failure, Insulin",

author = "Franco Cosmi and Li Shen and Michela Magnoli and Abraham, {William T.} and Anand, {Inder S.} and Cleland, {John G.} and Cohn, {Jay N.} and Deborah Cosmi and {De Berardis}, Giorgia and Kenneth Dickstein and Franzosi, {Maria Grazia} and Lars Gullestad and Jhund, {Pardeep S.} and John Kjekshus and Lars K{\o}ber and Vito Lepore and Giuseppe Lucisano and Maggioni, {Aldo P.} and Serge Masson and McMurray, {John J.V.} and Antonio Nicolucci and Vito Petrarolo and Fabio Robusto and Lidia Staszewsky and Luigi Tavazzi and Roberto Teli and Gianni Tognoni and John Wikstrand and Roberto Latini",

year = "2018",

doi = "10.1002/ejhf.1146",

language = "English",

volume = "20",

pages = "888--895",

journal = "European Journal of Heart Failure, Supplement",

issn = "1567-4215",

publisher = "JohnWiley & Sons Ltd",

number = "5",

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TY - JOUR

T1 - Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes

AU - Cosmi, Franco

AU - Shen, Li

AU - Magnoli, Michela

AU - Abraham, William T.

AU - Anand, Inder S.

AU - Cleland, John G.

AU - Cohn, Jay N.

AU - Cosmi, Deborah

AU - De Berardis, Giorgia

AU - Dickstein, Kenneth

AU - Franzosi, Maria Grazia

AU - Gullestad, Lars

AU - Jhund, Pardeep S.

AU - Kjekshus, John

AU - Køber, Lars

AU - Lepore, Vito

AU - Lucisano, Giuseppe

AU - Maggioni, Aldo P.

AU - Masson, Serge

AU - McMurray, John J.V.

AU - Nicolucci, Antonio

AU - Petrarolo, Vito

AU - Robusto, Fabio

AU - Staszewsky, Lidia

AU - Tavazzi, Luigi

AU - Teli, Roberto

AU - Tognoni, Gianni

AU - Wikstrand, John

AU - Latini, Roberto

PY - 2018

Y1 - 2018

N2 - Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.

AB - Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.

KW - Diabetes mellitus

KW - Heart failure

KW - Insulin

U2 - 10.1002/ejhf.1146

DO - 10.1002/ejhf.1146

M3 - Journal article

C2 - 29488676

AN - SCOPUS:85042564501

SN - 1567-4215

VL - 20

SP - 888

EP - 895

JO - European Journal of Heart Failure, Supplement

JF - European Journal of Heart Failure, Supplement

IS - 5

ER -

Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes

Abstract

Keywords

UN SDGs

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